OBJECTIVE: Renal fibrosis is a common feature in various chronic kidney diseases (CKD). Tubular cell damage is a main characterization which results from dysregulated fatty acid oxidation (FAO) and lipid accumulation. Cannabinoid Receptor 2 (CB2) contributes to renal fibrosis, however, its role in FAO dysregulation in tubular cells is not clarified. In this study, we found CB2 plays a detrimental role in lipid metabolism in tubular cells.
METHODS: CB2 knockout mice were adopted to establish a folic acid-induced nephropathy (FAN) model. CB2-induced FAO dysfunction, lipid deposition, and fibrogenesis were assessed in vivo and vitro. To explore molecular mechanisms, β-catenin inhibitors and peroxisome proliferator-activated receptor alpha (PPARα) activators were also used in CB2-overexpressed cells. The mediative role of β-catenin in CB2-inhibited PPARα and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) activation was analyzed.
RESULTS: CB2 activates β-catenin signaling, resulting in the suppression of PPARα/PGC-1α axis. This decreased FAO functions and led to lipid droplet formation in tubular cells. CB2 gene ablation effectively mitigated FAO dysfunction, lipid deposition and uremic toxins accumulation in FAN mice, consequently retarding renal fibrosis. Additionally, inhibition to β-catenin or PPARα activation could greatly inhibit lipid accumulation and fibrogenesis induced by CB2.
CONCLUSIONS: This study highlights CB2 disrupts FAO in tubular cells through β-catenin activation and subsequent inhibition on PPARα/PGC-1α activity. Targeted inhibition on CB2 offers a perspective therapeutic strategy to fight against renal fibrosis.

UNASSIGNED: Flexible cavovarus deformity is prevalent and the Coleman block test is frequently used to assess the first ray plantarflexion malpositioning in the overall deformity as well as the flexibility of the hindfoot. The objective was to assess and compare the weightbearing computed tomography (WBCT) 3-dimensional (3D) changes in clinical and bone alignment in flexible cavovarus deformity patients when performing the Coleman block test when compared to normal standing position and to controls.
UNASSIGNED: Twenty patients (40 feet) with flexible cavovarus deformity and 20 volunteer controls (40 feet) with normal foot alignment underwent WBCT imaging of the foot and ankle. Cavovarus patients were assessed in normal orthostatic and Coleman block test positions. Foot and ankle offset (FAO), hindfoot alignment angle (HAA), talocalcaneal angle (TCA), subtalar vertical angle (SVA) and talonavicular coverage angle (TNCA) and a CT-simulated soft tissue envelope image, WBCT clinical hindfoot alignment angle (WBCT-CHAA), were evaluated by 2 readers. Measurements were compared between cavovarus nonstressed and stressed positions and to controls. P values of .05 or less were considered significant.
UNASSIGNED: The intra- and interobserver intraclass correlation coefficient were good or excellent for all WBCT measurements. Cavovarus patients demonstrated significant correction of WBCT-CHAA (9.7 ± 0.4 degrees), FAO (2.6 ± 0.4%), and TNCA (8.8 ± 1.8 degrees) when performing the Coleman block test (all P values <.0001). However, WBCT-CHAA and FAO measurements were still residually deformed and significantly different from controls (P values of .001 and <.0001, respectively). TNCA values corrected to values similar to healthy controls (P = .29). No differences were observed in cavovarus patients during Coleman block test for the coronal measures: HAA, TCA, and SVA measurements.
UNASSIGNED: In this study, we observed improvement in the overall 3D WBCT alignment (FAO), axial plane adduction deformity (TNCA), as well as CT simulated clinical hindfoot alignment (WBCT-CHAA) in flexible cavovarus deformity patients when performing a Coleman block test. However, we did not find improvement in measures of coronal alignment of the hindfoot, indicating continued varus positioning of the hindfoot in these patients.
UNASSIGNED: Level III, retrospective comparative study.

Mitochondrial metabolism plays a central role in the regulation of hematopoietic stem cell (HSC) biology. Mitochondrial fatty acid oxidation (FAO) is pivotal in controlling HSC self-renewal and differentiation. Herein, we discuss recent evidence suggesting that NADPH generated in the mitochondria can influence the fate of HSCs. Although NADPH has multiple functions, HSCs show high levels of NADPH that are preferentially used for cholesterol biosynthesis. Endogenous cholesterol supports the biogenesis of extracellular vesicles (EVs), which are essential for maintaining HSC properties. We also highlight the significance of EVs in hematopoiesis through autocrine signaling. Elucidating the mitochondrial NADPH-cholesterol axis as part of the metabolic requirements of healthy HSCs will facilitate the development of new therapies for hematological disorders.

The complex pathogenesis of kidney disease is closely related to the diversity of kidney intrinsic cells. In this study, single-cell transcriptome sequencing technology was used to sequence and analyze blood and kidney tissue cells in normal control rats and rats with chronic kidney disease (CKD), focusing on key cell populations and functional enrichment to explore the pathogenesis of CKD. Oil red O staining and enzyme-linked immunosorbent assay (ELISA) were used to detect lipid droplets and free fatty acid (FFA). Quantitative real-time polymerase chain reaction (RT-PCR), western blot (WB) were used to verify the differential gene hydroxyacid oxidase 2 (HAO2) and fatty acid metabolic process in tissue to ensure the reliability of single-cell sequencing results. We successfully established a single-cell transcriptome atlas of blood and kidney tissue in rats with CKD, which were annotated into 14 cell subsets (MPCs, PT, Tc, DCT, B-IC, A-IC, CNT, ALOH, BC, Neu, Endo, Pla, NKT, Baso) according to marker gene, and the integrated single-cell atlas of rats showed a significant increase and decrease of MPCs and PTs in the CKD group, respectively. Functional analysis found extensive enrichment of metabolic-related pathways in PT cells, includes fatty acid metabolic process, cellular amino acid metabolic process and generation of precursor metabolites and energy. Immunohistochemical experiments determined that the differential gene HAO2 was localized in the renal tubules, and its expression was significantly reduced in CKD group compared with control, and oil red O staining showed that lipid droplets increased in the CKD group, after overexpression of HAO2 the lipid droplets was inhibited. ELISA assay showed that ATP content decreased in the CKD group and FFA increased in the CKD group. Moreover, the mitochondrial membrane potential of the cells in the OE-HAO2 group was significantly increased compared with OE-NC. The acyl-CoA oxidase 1(ACOX1), peroxisome proliferator-activated receptor alpha (PPARα), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) were decreased in the CKD group, while genes and proteins were increased after overexpression of HAO2, and the AMP-activated protein kinase (AMPK) phosphorylated proteins were increased, the acetyl-CoA carboxylase (ACC) phosphorylated proteins were decreased, reversely. Therefore, HAO2 may be an important regulator of fatty acid metabolic processes in CKD, and overexpression of HAO2 can enhance fatty acid metabolism by promoting fatty acid oxidation (FAO) pathway.

Mycobacterium tuberculosis (Mtb) successfully thrives in the host by adjusting its metabolism and manipulating the host environment. In this study, we investigated the role of Rv0547c, a protein that carries mitochondria-targeting sequence (MTS), in mycobacterial persistence. We show that Rv0547c is a functional oxidoreductase that targets host-cell mitochondria. Interestingly, the localization of Rv0547c to mitochondria was independent of the predicted MTS but depended on specific arginine residues at the N- and C-terminals. As compared to the mitochondria-localization defective mutant, Rv0547c-2SDM, wild-type Rv0547c increased mitochondrial membrane fluidity and spare respiratory capacity. To comprehend the possible reason, comparative lipidomics was performed that revealed a reduced variability of long-chain and very long-chain fatty acids as well as altered levels of phosphatidylcholine and phosphatidylinositol class of lipids upon expression of Rv0547c, explaining the increased membrane fluidity. Additionally, the over representation of propionate metabolism and β-oxidation intermediates in Rv0547c-targeted mitochondrial fractions indicated altered fatty acid metabolism, which corroborated with changes in oxygen consumption rate (OCR) upon etomoxir treatment in HEK293T cells transiently expressing Rv0547c, resulting in enhanced mitochondrial fatty acid oxidation capacity. Furthermore, Mycobacterium smegmatis over expressing Rv0547c showed increased persistence during infection of THP-1 macrophages, which correlated with its increased expression in Mtb during oxidative and nutrient starvation stresses. This study identified for the first time an Mtb protein that alters mitochondrial metabolism and aids in survival in host macrophages by altering fatty acid metabolism to its benefit and, at the same time increases mitochondrial spare respiratory capacity to mitigate infection stresses and maintain cell viability.

BACKGROUND: 2,3,5,4\'-tetrahydroxy-stilbene-2-O-β-D-glucoside (TSG) is the principal bioactive compound contained in Polygonum multiflorum Thunb. (PMT), which is traditionally recorded to possess tonic and anti-aging efficacy.
OBJECTIVE: To identify the TSG-provided promotion on liver regeneration (LR) following partial hepatectomy (PHx) in mice and to explicate its involved mechanism.
METHODS: The promotion of TSG on LR was evaluated by hematoxylin and eosin (H&E), 5-bromodeoxyuridinc (BrdU) and Ki-67 staining, and measuring the level of proliferating cell nuclear antigen (PCNA) and Cyclin D1 in mice with PHx at different time points. Gene Expression Omnibus (GEO, GSE15239) database and the label-free quantitative proteomics from liver of mice at 24 h after PHx were integrated to identify potential involved critical proteins, which were verified by Western-blot, Real-time polymerase chain reaction (RT-PCR), molecular docking and luciferase activity assay. Primary hepatocytes isolated from mice were used to investigate the TSG-provided promotion on proliferation in vitro.
RESULTS: TSG (20 mg/kg) promoted LR in mice after PHx. Results from RNA expression data from clinical samples and proteomic analysis from liver tissues indicated that peroxisome proliferator-activated receptor α (PPARα)-mediated fatty acid metabolism pathway were crucially associated with the TSG-provided promotion on LR. TSG enhanced the nuclear translocation of PPARα and the mRNA expression of a series of PPARα-regulated downstream genes. In addition, TSG lowered hepatic triglyceride (TG) and non-esterified fatty acid (NEFA) amounts and increased hepatic adenosine triphosphate (ATP) level in mice after PHx. TSG up-regulated the transcriptional activity of PPARα in vitro. Next results displayed that TSG promoted cell proliferation as well as ATP level in mice primary hepatocytes, which were abolished when PPARα was suppressed. Meanwhile, the cell viability was also elevated in mice primary hepatocytes treated with ATP.
CONCLUSIONS: Activating PPARα-mediated fatty acid β-oxidation (FAO) pathway led to the production of ATP, which contributed to the TSG-provided promotion on LR after PHx in mice.

Oxidative stress plays a pivotal role in the development of diabetic cardiomyopathy (DCM). Previous studies have revealed that inhibition of mitochondrial fission suppressed oxidative stress and alleviated mitochondrial dysfunction and cardiac dysfunction in diabetic mice. However, no research has confirmed whether mitochondria fission accentuates hyperglycemia-induced cardiomyoblast oxidative stress through regulating fatty acid oxidation (FAO). We used H9c2 cardiomyoblasts exposed to high glucose (HG) 33 mM to simulate DCM in vitro. Excessive mitochondrial fission, poor cell viability, and lipid accumulation were observed in hyperglycemia-induced H9c2 cardiomyoblasts. Also, the cells were led to oxidative stress injury, lower adenosine triphosphate (ATP) levels, and apoptosis. Dynamin-related protein 1 (Drp1) short interfering RNA (siRNA) decreased targeted marker expression, inhibited mitochondrial fragmentation and lipid accumulation, suppressed oxidative stress, reduced cardiomyoblast apoptosis, and improved cell viability and ATP levels in HG-exposed H9c2 cardiomyoblasts, but not in carnitine palmitoyltransferase 1 (CPT1) inhibitor etomoxir treatment cells. We also found subcellular localization of CPT1 on the mitochondrial membrane, FAO, and levels of nicotinamide adenine dinucleotide phosphate (NADPH) were suppressed after exposure to HG treatment, whereas Drp1 siRNA normalized mitochondrial CPT1, FAO, and NADPH. However, the blockade of FAO with etomoxir abolished the above effects of Drp1 siRNA in hyperglycemia-induced H9c2 cardiomyoblasts. The preservation of mitochondrial function through the Drp1/CPT1/FAO pathway is the potential mechanism of inhibited mitochondria fission in attenuating oxidative stress injury of hyperglycemia-induced H9c2 cardiomyoblasts.

The ocular surface is a mucosal barrier tissue colonized by commensal microbes, which tune local immunity by eliciting IL-17 from conjunctival γδ T cells to prevent pathogenic infection. The commensal Corynebacterium mastitidis (C. mast) elicits protective IL-17 responses from conjunctival Vγ4 T cells through a combination of γδ TCR ligation and IL-1 signaling. Here, we identify Vγ6 T cells as a major C. mast-responsive subset in the conjunctiva and uncover its unique activation requirements. We demonstrate that Vγ6 cells require not only extrinsic (via dendritic cells) but also intrinsic TLR2 stimulation for optimal IL-17A response. Mechanistically, intrinsic TLR2 signaling was associated with epigenetic changes and enhanced expression of genes responsible for metabolic shift to fatty acid oxidation to support Il17a transcription. We identify one key transcription factor, IκBζ, which is upregulated by TLR2 stimulation and is essential for this program. Our study highlights the importance of intrinsic TLR2 signaling in driving metabolic reprogramming and production of IL-17A in microbiome-specific mucosal γδ T cells.

Triple-negative breast cancer (TNBC), the most aggressive subtype of breast cancer, has a poor prognosis and lacks effective treatment strategies. Here, the study discovered that TNBC shows a decreased expression of epithelial transcription factor ovo-like 2 (OVOL2). The loss of OVOL2 promotes fatty acid oxidation (FAO), providing additional energy and NADPH to sustain stemness characteristics, including sphere-forming capacity and tumor initiation. Mechanistically, OVOL2 not only suppressed STAT3 phosphorylation by directly inhibiting JAK transcription but also recruited histone deacetylase 1 (HDAC1) to STAT3, thereby reducing the transcriptional activation of downstream genes carnitine palmitoyltransferase1 (CPT1A and CPT1B). PyVT-Ovol2 knockout mice develop a higher number of primary breast tumors with accelerated growth and increased lung-metastases. Furthermore, treatment with FAO inhibitors effectively reduces stemness characteristics of tumor cells, breast tumor initiation, and metastasis, especially in OVOL2-deficient breast tumors. The findings suggest that targeting JAK/STAT3 pathway and FAO is a promising therapeutic strategy for OVOL2-deficient TNBC.

UNASSIGNED: Due to the several interconnected crises that Lebanon has been facing for the past 4 years, many important social and environmental issues have been overlooked until more \"pressing\" ones are dealt with. Consequently, water pollution in Lebanon continues to worsen.
UNASSIGNED: This study aimed to describe the microbiological and chemical properties of the 10 main rivers in Lebanon and to assess their suitability for irrigation, while exploring some of the solutions to the problem.
UNASSIGNED: This cross-sectional study evaluated the pollution level of water from 10 rivers in Lebanon in June 2023 and their suitability for irrigation. Samples were collected at 3°C and their quality parameters were measured. Statistical analysis was conducted using R statistical software version 4.0.2.
UNASSIGNED: Compared to the Food and Agriculture Organization (FAO) guidelines for safe irrigation water use, 4 out of the 10 samples had pH levels exceeding the permissible threshold, resulting in severe limitations on their usability. Three rivers had nitrate concentrations that exceeded the approved range, thus constraining their severe usage. Among the rivers, 60% had Escherichia coli levels higher than the permissible spectrum and 40% had faecal coliform counts exceeding FAO\'s upper limit recommendation. All water sources, however, had total dissolved solid levels that were within the recommended range.
UNASSIGNED: Polluted water can have a negative impact on human, wildlife and ecosystem health. Most of the assessed rivers in our study contained bacterial colonies, above the maximum recommended internationally. There is therefore an urgent need to address pollution issues in Lebanese waters to make them suitable for irrigation and other uses.
تلوُّث مياه الأنهار في لبنان: المشكلة الصحية العامة المستهون بها بشدة في البلد.
كارولا الشامية، كلوديا الحداد، خالد الخطيب، إدموند جلخ، فيكتوريا الكراكي، جانا زين الدين، أنطوان عساف، تانيا حارب، إيلي بو سناء.
UNASSIGNED: نظرًا للأزمات المترابطة العديدة التي يواجهها لبنان منذ 4 سنوات (منذ 2019)، جرى تجاهل العديد من القضايا الاجتماعية والبيئية المهمة من أجل التعامل مع القضايا الأخرى الأكثر \"إلحاحًا\". ونتيجة لذلك، لا يزال تلوُّث المياه في لبنان يتفاقم.
UNASSIGNED: هدفت هذه الدراسة إلى وصف الخصائص الميكروبيولوجية والكيميائية للأنهار الرئيسية العشرة في لبنان وتقييم مدى ملاءمتها للري، مع استكشاف بعض الحلول للمشكلة.
UNASSIGNED: قيَّمت هذه الدراسة المقطعية مستوى تلوُّث المياه المأخوذة من 10 أنهار في لبنان في يونيو/حزيران 2023 ومدى ملاءمتها للري. وجُُمعت العينات في درجة حرارة 3 درجات مئوية وقِيسَت بارامترات جودتها. وأُجريَ تحليل إحصائي بالإصدار 4,0,2 من برنامج R الإحصائي.
UNASSIGNED: مقارنةً بالمبادئ التوجيهية لمنظمة الأغذية والزراعة (الفاو) بشأن استخدام مياه الري المأمونة، كانت مستويات درجة الحموضة في 4 عينات من أصل 10 عينات تتجاوز الحدَّ الأدنى المسموح به، وهو ما أدى إلى وجود قيود شديدة على إمكانية استخدامها. وفي ثلاثة أنهار تركيزاتٌ من النترات تتجاوز النطاق المعتمد، الأمر الذي يحد من استخدامها بشدة. ومن بين الأنهار، كان لدى 60٪ منها مستويات من الإشريكية القولونية أعلى من النطاق المسموح به، وكان لدى 40٪ منها أعداد من القولونيات البرازية تتجاوز الحد الأقصى الذي أوصت به منظمة الأغذية والزراعة. غير أن مستويات إجمالي المواد الصلبة المذابة في جميع مصادر المياه تقع ضمن النطاق المُوصى به.
UNASSIGNED: يمكن أن يكون للمياه الملوثة تأثير سلبي على صحة الإنسان والحياة البرية والنظام الإيكولوجي. وتحتوي معظم الأنهار التي قُيِّمت في دراستنا على مستعمرات بكتيرية بما يتجاوز الحد الأقصى المُوصى به دوليًّا. ولذلك هناك حاجة ملحة لمعالجة قضايا التلوث في المياه اللبنانية لجعلها مناسبة للري والاستخدامات الأخرى.
Pollution des cours d\'eau au Liban : le problème de santé publique le plus sous-estimé du pays.
UNASSIGNED: En raison des nombreuses crises interdépendantes auxquelles le Liban a dû faire face au cours des quatre dernières années, certaines problématiques sociales et environnementales ont été négligées au profit d\'autres jugées plus « importantes ». En conséquence, la pollution de l\'eau au Liban continue de s\'intensifier.
UNASSIGNED: La présente étude visait à décrire les propriétés microbiologiques et chimiques des 10 principaux cours d\'eau du Liban et à évaluer si elles sont adaptées à l\'irrigation, tout en examinant certaines solutions au problème.
UNASSIGNED: La présente étude transversale a évalué le niveau de pollution de 10 cours d\'eau au Liban en juin 2023 et a déterminé s\'ils sont adaptés à l\'irrigation. Les échantillons ont été prélevés à une température de 3 °C et leurs paramètres de qualité ont été mesurés. Une analyse statistique a été réalisée à l\'aide du logiciel de statistiques R version 4.0.2.
UNASSIGNED: Par rapport aux lignes directrices de l\'Organisation des Nations Unies pour l\'alimentation et l\'agriculture (FAO) concernant l\'utilisation sûre de l\'eau d\'irrigation, quatre des 10 échantillons présentaient des taux de pH supérieurs au seuil autorisé, entraînant de sévères limitations quant à l\'utilisabilité de ces eaux. Trois cours d\'eau présentaient des concentrations de nitrate supérieures à la fourchette autorisée, ce qui limitait leur utilisation intensive. Soixante pour cent des cours d\'eau affichaient des niveaux d\'Escherichia coli supérieurs à la fourchette autorisée et 40 % enregistraient un nombre de coliformes fécaux excédant la limite maximale recommandée par la FAO. Cependant, tous les cours d\'eau présentaient des niveaux totaux de solides dissous compris dans la fourchette recommandée.
UNASSIGNED: L\'eau polluée peut avoir un impact négatif sur la santé des humains, des espèces sauvages et des écosystèmes. La plupart des cours d\'eau évalués dans notre étude contenaient un nombre de colonies bactériennes supérieur au seuil maximal recommandé à l\'échelle internationale. Il est donc urgent de remédier aux problèmes de pollution des eaux au Liban afin de les rendre aptes à l\'irrigation et à d\'autres usages.